1. Field of the Invention
This invention relates to pharmaceutical preparations for administration by percutaneous absorption that contain Nicorandil and to a method for their manufacture. More particularly, it relates to pharmaceutical preparations for administration by percutaneous absorption such as tapes and/or sheets (hereinafter refer to as tapes) and ointments, etc., that have excellent absorbability through the skin and that moreover are very stable in terms of the ingredients of the pharmaceutical agents contained therein.
2. Description of the Prior Art
Nicorandil, or N-(2-hydroxyethyl)nicotinamide nitrate, is an effective drug for the treatment of angina pectoris caused by many kinds of disorders, as it acts to dilate the coronary vessels and to inhibit contractions of the coronary veins, without much effect on the blood flow through the heart or on heart function (Japanese Patent Publication 58-17463). This Nicorandil is commercially available as a drug to be taken orally. However, in general, when a drug is taken orally, its rate of absorption varies according to the conditions in the stomach and the intestines, such as the pH, the present or absence of other contents, etc., and so it is difficult for the drug to be absorbed gradually at a steady rate over a long period of time. When the Nicorandil mentioned above is given orally, it sometimes causes side effects such as orthostatic hypotension and headache, caused when there is a rapid increase of the level of this agent in the blood.
It is known that some drugs for which it is difficult to achieve a uniform rate of absorption by the oral route can be given in the form of a pharmaceutical preparation with administration by percutaneous absorption. One typical drug for angina pectoris is a preparation of nitroglycerin in tape form (Japanese Patent Laid-Open 56-133381). A preparation of the Nicorandil mentioned above in tape form has also been proposed. For example, in Japanese Patent Laid-Open 59-10513, it has been proposed that a polymer with a glass transition point, T.sub.g, of -70.degree. to -10.degree. C. and with the property of adhesion with pressure at ordinary temperatures be bound to Nicorandil, and that this pharmaceutical preparation be made into tape form by being layered onto a support.
In the pharmaceutical preparation in tape form disclosed in Japanese Patent Laid-Open 59-10513 mentioned above, the basic necessary conditions are given, such as that the structure of the polymer that makes up the base material must be suitably compatible with the Nicorandil, that the greater part of the Nicorandil must not become crystallized in the base material, that the Nicorandil is supplied from the base material at a rate suitable for absorption into the skin, etc. However, Nicorandil is relatively unstable at conditions of high temperature or high humidity, or in solution (Iyakuhin Kenkyu, vol. 14 (issue 6), pp. 968-979, 1983), and among the agents absorbed percutaneously that satisfy the conditions mentioned above in the report, Nicorandil is extremely unstable, and the stability during storage for long periods of time needed for pharmaceutical preparations cannot be ensured.